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Vrtinčnoslojno granuliranje je danes ena najpogosteje uporabljenih metod izdelave zrnc v farmacevtski industriji. V okviru magistrske naloge smo ovrednotili vpliv izbranih procesnih parametrov vrtinčnoslojnega granuliranja na fizikalne lastnosti izdelanih zrnc. V prvem sklopu smo na placebo poskusih vrednotili vpliv velikosti serije ob enakem % napolnjenosti 3 L, 6 L in 12 L granulacijskih posod, različnih velikosti serije in tako različnih % napolnjenosti 3 L posode, lege šobe, hitrosti dovajanja granulacijske tekočine in koncentracije polimera v granulacijski tekočini. Ugotovili smo izrazit vpliv velikosti serije ob ohranjenem % napolnjenosti posode in ustrezni prilagoditvi procesnih parametrov. Zrnca, izdelana v najmanjši (3 L) posodi, so bila najmanjša in so imela najožjo porazdelitev velikosti, zrnca, izdelana v največji posodi (12 L) pa največja z najširšo porazdelitvijo velikosti. Ugotovili smo tudi, da smo ob spremenjenem % napolnjenosti večja zrnca dobili pri poskusu z manjšim % napolnjenosti granulacijske posode. Lega šobe je pomembno vplivala na učinkovitost granuliranja, saj je bil večji del praškastih nezgranuliranih delcev pri poskusu, kjer je bila šoba v nižji legi. Večja kot je bila hitrost dovajanja granulacijske tekočine, večja so bila izdelana zrnca. Prav tako smo opazili vpliv koncentracije polimera v granulacijski tekočini na lastnosti zrnc, saj smo dobili večja zrnca pri poskusu, kjer smo uporabili bolj koncentrirano granulacijsko tekočino. Na osnovi placebo poskusov smo določili optimalne procesne parametre granuliranja za izvedbo drugega sklopa poskusov z modelno zdravilno učinkovino (MZU). Uporabili smo MZU z različno velikostjo delcev in na ta način ovrednotili vpliv velikosti delcev MZU na fizikalne lastnosti zrnc. Iz končnih zrnc smo nato pri različnih silah stiskanja izdelali tablete. Tabletam smo izmerili trdnost, razpadnost, krušljivost ter lom in s primerjavo rezultatov skušali ovrednotiti vpliv velikosti delcev MZU na lastnosti tablet. Pokazali smo, da velikost delcev MZU zelo vpliva na obnašanje začetne zmesi. Največja zrnca smo dobili pri poskusu, kjer smo uporabili najmanjše delce MZU, najmanjša pa pri poskusu, kjer smo uporabili največje delce MZU. Glede na primerljive rezultate trdnosti tablet z najmanjšimi in največjimi delci MZU, stisnjenih pri primerljivih silah stiskanja, smo sklepali, da velikost delcev MZU ne vpliva bistveno na trdnost tablet. Razpadnost vseh tablet se je z naraščanjem sile stiskanja daljšala. Najdaljši razpadni čas so imele tablete, izdelane iz zrnc, ki so vsebovala MZU z najmanjšimi delci. Krušljivost in lom tablet sta bila ustrezna pri vseh poskusih, ne glede na velikost delcev MZU. Fluid bed granulation is currently one of the most widely used methods for producing granules in the pharmaceutical industry. In the scope of the master's thesis, we evaluated the influence of selected process parameters of fluid-bed granulation on the physical properties of the produced granules. In the first set of experiments on placebo batches, we evaluated the impact of batch size at the same percentage of filling in 3L, 6L, and 12L granulation vessels, different batch sizes and consequently different percentages of filling in the 3L granulation vessel, nozzle position, granulation liquid feeding rate, and polymer concentration in the granulation liquid using placebo trials. We found a significant influence of batch size while maintaining the same percentage of vessel filling and appropriate adjustment of process parameters. The granules produced in the smallest (3L) vessel were the smallest and had the narrowest size distribution, while the granules produced in the largest vessel (12L) were the largest with the widest size distribution. We also found that changing the percentage of vessel filling resulted in larger granules when using a lower percentage of vessel filling. The nozzle position had a significant impact on the granulation efficiency, as a larger portion of powdery ungranulated particles was observed when the nozzle was in a lower position. Increasing the spray rate of granulation liquid resulted in larger granules. Additionally, we observed the influence of polymer concentration in the granulation liquid on the properties of the granules, as larger granules were obtained when using a more concentrated granulation liquid. Based on placebo samples, we determined the optimal process parameters for granulation to conduct the second set of experiments with a model active pharmaceutical ingredient (API). We used APIs with different particle sizes to evaluate the influence of API particle size on the physical properties of the granules. Tablets were then prepared from the final granules at different compression forces. The tablets were tested for hardness, disintegration, friability, and prolonged friability, and the results were compared to evaluate the impact of API particle size on the tablet properties. We demonstrated that API particle size has a significant effect on the behavior of the initial mixture. The largest granules were obtained when using the smallest API particles, while the smallest granules were obtained when using the largest API particles. Considering the comparable tablet hardness results with the smallest and largest API particles compressed at different compression forces, we concluded that API particle size does not have a substantial impact on tablet hardness. However, the disintegration time of all tablets increased with increasing compression force. The tablets made from granules containing the smallest API particles had the longest disintegration time. Friability and prolonged friability of the tablets were acceptable in all experiments regardless of the API particle size. |
